Journal of Physiology and Biochemistry

, Volume 67, Issue 1, pp 121–128 | Cite as

Inhibitory effects of estrogens on digestive enzymes, insulin deficiency, and pancreas toxicity in diabetic rats

  • Khaled HamdenEmail author
  • Bassem Jaouadi
  • Nedia Zaraî
  • Tarek Rebai
  • Serge Carreau
  • Abdelfattah Elfeki
Original Paper


Diabetes mellitus, with its attendant disorders and dysfunctional behaviors, constitutes a growing concern to the population of the world. With this concern in mind, the present study investigated the anti-diabetic and hypolipedimic potential of 17β-estradiol (called E2), particularly in terms of its inhibitory effects on maltase, sucrase, lactase, and lipase activities in the intestine of surviving diabetic rats. The findings revealed that this supplement helped protect the β cells of the rats from death and damage. Interestingly, E2 induced considerable decreases of 29%, 46%, 42%, and 84% in the activities of intestinal maltase, lactase, sucrase, and lipase, respectively. The E2 extract also decreased the glucose, triglyceride, and total cholesterol rates in the plasma of diabetic rats by 39%, 27%, and 53%, respectively, and increased the HDL–cholesterol level by 74%, which helped maintain the homeostasis of blood lipid. When compared to those of the untreated diabetic rats, the superoxide dismutase, catalase, and glutathione peroxidase levels in the pancreas of the rats treated with this supplement were also enhanced by 330%, 170%, and 301%, respectively. A significant decrease was also observed in the lipid peroxidation level and lactate dehydrogenase activity in the pancreas of diabetic rats after E2 administration. Overall, the findings presented in this study demonstrate that E2 has both a promising potential with regard to the inhibition of intestinal maltase, sucrase, lactase, and lipase activities, and a valuable hypoglycemic and hypolipidemic function, which make it a potential strong candidate for industrial application as apharmacological agent for the treatment and prevention of hyperlipidemia, obesity, and cardiovascular diseases.


Disaccharidases Lipase Intestine Estrogens Diabetes Pancreas 



This research was supported by the Tunisian Ministry of Higher Education and Scientific Research and Technology and the Tunisian Ministry of Public Health. The authors wish to express their sincere gratitude to Prof. Anouar Smaoui from the English department at the Faculty of Science of Sfax for carefully proofreading and polishing the language of the present paper.


  1. 1.
    Aebi H (1984) Catalase in vitro. Meth Enzymol 105:121–126CrossRefPubMedGoogle Scholar
  2. 2.
    Buege JA, Aust SD (1967) Microsomal lipid peroxidation. Meth Enzymol 105:302–310Google Scholar
  3. 3.
    Dahlqvist A (1968) Assay of intestinal disaccharidases. Anal Biochem 22:99–107CrossRefPubMedGoogle Scholar
  4. 4.
    Fonseca V (2003) Clinical significance of targeting postprandial and fasting hyperglycemia in managing type 2 diabetes mellitus. Curr Med Res Opin 19:635–641CrossRefPubMedGoogle Scholar
  5. 5.
    González-Gil EM, Bueno-Lozano G, Bueno-Lozano O, Moreno LA, Cuadrón-Andres L, Huerta-Blas P, Garagorri JM, Bueno M (2009) Serum transaminases concentrations in obese children and adolescents. J Physiol Biochem 65:51–60CrossRefPubMedGoogle Scholar
  6. 6.
    Hamden K, Carreau S, Jamoussi K, Ayadi F, Garmazi F, Elfeki A (2008) Inhibitory effects of 1α, 25dihydroxyvitamin D3 and Ajuga iva extract on oxidative stress, toxicity and hypo-fertility in diabetic rat testes. J Physiol Biochem 64:231–240PubMedGoogle Scholar
  7. 7.
    Hamden K, Carreau S, Lajmi S, Aloulou D, Kchaou D, Elfeki A (2008) Protective effect of 17β-estradiol on hyperglycemia, stress oxidant, liver dysfunction and histological changes induced by alloxan in male rat pancreas and liver. Steroids 94:495–501CrossRefGoogle Scholar
  8. 8.
    Hamden K, Allouche N, Damak M, Elfeki A (2009) Hypoglycemic and antioxidant effects of phenolic extracts and purified hydroxytyrosol from olive mill waste in-vitro and in rats. Chem Biol Interact. doi: 10.1016/j.cbi.2009.04.002 PubMedGoogle Scholar
  9. 9.
    Hamden K, Ayadi F, Jamoussi K, Masmoudi H, Elfeki A (2009) Therapeutic effect of phytoecdysteroids rich extract from Ajuga iva on alloxan induced diabetic rats liver, kidney and pancreas. Biofactors 33:1–12Google Scholar
  10. 10.
    Heo SJ, Hwang JY, Choi JI, Han JS, Kim HJ, Jeon YJ (2009) Diphlorethohydroxycarmalol isolated from Ishige okamurae, brown algae, a potent α-glucosidase and α-amylase inhibitor, alleviates postprandial hyperglycemia in diabetic mice. Eur J Pharmacol. doi: 10.1016/j.ejphar.2009.05.017 PubMedGoogle Scholar
  11. 11.
    Khookhor O, Bolin Q, Oshida Y, Sato Y (2007) Effect of Mongolian plants on in vivo insulin action in diabetic rats. Diab Res Clin Pract 75:135–140CrossRefGoogle Scholar
  12. 12.
    Kim KY, Nam KA, Kurihara H, Kim SM (2008) Potent α-glucosidase inhibitors purified from the red alga Grateloupia elliptica. Phytochemistry 69:2820–2825CrossRefPubMedGoogle Scholar
  13. 13.
    Kowluru RA, Chan PS (2007) Oxidative stress and diabetic retinopathy. Exp Diab Res. doi: 10.1155/2007/43603 Google Scholar
  14. 14.
    Le May C, Chu K, Hu M, Ortega CS, Simpson ER, Korach KS, Tsai MJ, Mauvais-Jarvis F (2006) Estrogens protect pancreatic β-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice. Proc Natl Acad Sci USA 103:9232–9237CrossRefPubMedGoogle Scholar
  15. 15.
    Lee DS, Lee SH (2001) Genistein, a soy isoflavone, is a potent α-glucosidase inhibitor. FEBS Lett 501:84–86CrossRefPubMedGoogle Scholar
  16. 16.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1955) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  17. 17.
    Marklund S, Marklund G (1975) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474CrossRefGoogle Scholar
  18. 18.
    McCue P, Kwon YI, Shetty K (2005) Anti-diabetic and anti-hypertensive potential of sprouted and solid-state bioprocessed soybean. Asia Pac J Clin Nutr 14:145–152PubMedGoogle Scholar
  19. 19.
    Mccue P, Kwon YI, Shetty K (2005) Anti-amylase, anti-glucosidase and anti-angiotensin I-converting enzyme potential of selected foods. J Food Biochem 29:278–294CrossRefGoogle Scholar
  20. 20.
    McDougall GJ, Stewart D (2005) The inhibitory effects of berry polyphenols on digestive enzymes. Biofactors 23:189–195CrossRefPubMedGoogle Scholar
  21. 21.
    O’Donovan C, Feinle-Bisset J, Horowitz M (2003) Lipase inhibition attenuates the acute inhibitory effects of oral fat on food intake in healthy subjects. Br J Nutr 90:849–855CrossRefPubMedGoogle Scholar
  22. 22.
    Pagila DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169Google Scholar
  23. 23.
    Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, Barber A, Martínez JA, Moreno-Aliaga MJ (2009) Lipoic acid prevents body weight gain induced by a high fat diet in rats: effects on intestinal sugar transport. J Physiol Biochem 65:43–50CrossRefPubMedGoogle Scholar
  24. 24.
    Sanclemente T, Marques-Lopes I, Puzo J, García-Otín AL (2009) Role of naturally-occurring plant sterols on intestinal cholesterol absorption and plasmatic levels. J Physiol Biochem 65:87–98CrossRefPubMedGoogle Scholar
  25. 25.
    Satouchi K, Hiranou K, Fujino O, Ikoma M, Tanaka T, Kitamura K (1998) Lipoxygenase-1 from soybean seed inhibiting the activity of pancreatic lipase. Biosci Biotechnol Biochem 62:1498–1503CrossRefPubMedGoogle Scholar
  26. 26.
    Shirpoor A, Ilkhanizadeh B, Saadatian R, Darvari BS, Behtaj F, Karimipour M, Ghaderi-Pakdel F, Saboori E (2006) Effect of vitamin E on diabetes-induced changes in small intestine and plasma antioxidant capacity in rat. J Physiol Biochem 62:171–178CrossRefPubMedGoogle Scholar
  27. 27.
    Singh R, Nagapaul JP, Majumdar S, Chakravarti RN, Dhall GI (1985) Effects of 17 beta-estradiol and progesterone on intestinal digestive and absorptive functions in ovariectomized rats. Biochem Int 101:777–786Google Scholar
  28. 28.
    Viña J, Borrás C, Gambini J, Sastre J, Pallardo FV (2005) Why females live longer than males? Importance of the upregulation of longevity-associated genes by oestrogenic compounds. FEBS Lett 579:2541–2545CrossRefPubMedGoogle Scholar
  29. 29.
    Viña J, Sastre J, Pallardó FV, Gambini J, Borrás C (2008) Modulation of longevity-associated genes by estrogens or phytoestrogens. Biol Chem 389:273–277CrossRefPubMedGoogle Scholar
  30. 30.
    Yoshikawa M, Shimoda H, Nishida N, Takada M, Matsuda H (2002) Salacia reticulata and its polyphenolic constituents with lipase inhibitory and lipolytic activities have mild antiobesity effects in rats. J Nutr 132:1819–1824PubMedGoogle Scholar
  31. 31.
    Zirilli L, Rochira V, Diazzi C, Caffagni G, Carani C (2008) Human models of aromatase deficiency. J Steroid Biochem Mol Biol 109:212–218CrossRefPubMedGoogle Scholar

Copyright information

© University of Navarra 2010

Authors and Affiliations

  • Khaled Hamden
    • 1
    • 2
    Email author
  • Bassem Jaouadi
    • 3
  • Nedia Zaraî
    • 3
  • Tarek Rebai
    • 4
  • Serge Carreau
    • 5
  • Abdelfattah Elfeki
    • 2
  1. 1.Biotechnology High School of Sfax (ISBS)SfaxTunisia
  2. 2.Laboratory of Animal Ecophysiology, Faculty of Science of SfaxSfaxTunisia
  3. 3.Laboratory of Microorganisms and Biomolecules, Centre of Biotechnology of SfaxSfaxTunisia
  4. 4.Laboratory of Histology–EmbryologyFaculty of Medicine of SfaxSfaxTunisia
  5. 5.Department of BiochemistryUniversity of Caen-Basse Normandie, USC INRACHU-CaenFrance

Personalised recommendations